The TCL1 Gene Is Involved, Other Than in Lymphoid Differentiation and Early Embryogenesis, Also in the Development of the Hair Follicle.

The TCL1(T-cell leukaemia lymphoma1) oncogene plays a causative role in the onset of T and B cell leukaemia of mature phenotype, such as T-prolymphocytic leukema T-(PLL) in human and mice and B-cell-chroni lymphatic leukaemia (B-CLL) in mice due to its overexpression. Moreover, Tcl1 −/− mice show that this gene is also important during the early embryogenesis and lymphocyte differentiation. An undiscovered role was found for TCL1 gene in the skin. In this work, we show evidences that give Tcl1 a new, important role in mouse hair follicle (HF) and skin homeostasis. In fact, Tcl1 −/− adult mice develop premature hair loss leading to alopecia followed by extensive skin lesions, starting from the dorsal region. The expression pattern of Tcl1 in the skin throughout the different stages of hair and skin differentiation, by in vivo immunofluorescence and fluorescent in situ hybridization experiments, shows a high level of the mRNA and protein in HF mainly in the secondary hair germ cells and hair bulge but not in dermal papilla (DP), both in early anagen and late catagen phases, and to less extent in the epidermis in all the stages examined.

Loss of Tcl1 expression in the skin, although initially does not show any apparent morphological defects in the HF and epidermis, nonetheless leads to an increased rate of apoptosis and to a parallel reduction of proliferation through an unknown pathway, independent from the phosphorylation of akt proteins. Indeed, we show evidences that loss of Tcl1 affects CD34 high expression level in the bulge stem cells that is necessary, to these population, to maintain slow-cycling and stem characteristics along the time. Finally, the higher expression of the Tcl1 ortholog Tcl1B2 in epidermis and hair bulb can further explain the late onset, in adult mice, of alopecia and skin lesions. Our findings suggest that Tcl1 gene(s) have important roles in cycling, self-renewing stem cell populations in skin. This observation, coupled with other previous work showing that TCL1 gene is expressed in B-cell entering the germinal follicle in the lymph-node and in the preimplantation embryo until the 8-cell stage, points out to an interesting role for this gene for cells that at some point in their life must re-enter cell cycle.